2,3-diacylated, 2- and 3-mono-acylated alkylated imino sugars exhibiting glucosidase inhibition and their method of use

Abstract

Described herein are alkylated imino sugars derivatives having a disease-modifying action in the treatment of diseases associated with glucosidase activity that include viral hemorrhagic fevers and other enveloped viruses, and any other diseases involving glucosidase activity.

What is claimed is: 
     
       1. A compound having formula (I): 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  and R 2  are independently selected from hydrogen and COR 5 ; and when R 1  is hydrogen, R 2  is not hydrogen; 
 R 3  is selected from hydrogen, optionally substituted C 1-6  alkyl, optionally substituted C 3-14  cycloalkyl, COR 6 , CO 2 R 7 , SO 2 R 8 , CONHR 9 , and P(O)(OR 10 ) 2 ; 
 R 4  is selected from hydrogen, optionally substituted C 1-6  alkyl, optionally substituted C 3-14  cycloalkyl, 1-adamantyl, 2-adamantyl, and optionally substituted aryl which may be substituted by 0-5 moieties; 
 R 4  and R 7  are taken together with the atom to which they are bound to form an optionally substituted ring having 5 ring atoms; 
 R 4  and R 7  are taken together with the atom to which they are bound to form 
 
       
         
           
           
               
               
           
         
       
       or
 R 4  and R 7  are taken together with the atom to which they are bound to form 
 
       
         
           
           
               
               
           
         
         R 5  is independently selected from optionally substituted C 3-14  cycloalkyl, optionally substituted aryl which may be substituted by 0-5 moieties, OR 13 , 
       
       
         
           
           
               
               
           
         
         R 6  is selected from optionally substituted C 1-10  alkyl, optionally substituted branched C 1-10  alkyl, optionally substituted C 3-14  cycloalkyl, and optionally substituted aryl which may be substituted by 0-5 moieties; 
         R 7  is selected from optionally substituted C 1-10  alkyl, optionally substituted C 3-14  cycloalkyl, and optionally substituted branched C 1-6  alkyl; 
         R 8  is selected from optionally substituted C 1-10  alkyl, optionally substituted branched C 1-10  alkyl, optionally substituted C 3-14  cycloalkyl, and optionally substituted aryl which may be substituted by 0-5 moieties; 
         R 9  is selected from hydrogen, optionally substituted C 1-10  alkyl, optionally substituted branched C 1-10  alkyl, optionally substituted C 3-14  cycloalkyl, and optionally substituted aryl which may be substituted by 0-5 moieties; 
         R 10  is selected from optionally substituted C 1-10  alkyl, optionally substituted branched C 3-10 , and optionally substituted cyclic C 3-14  cycloalkyl; 
         R 11a , R 11b , R 11c , and R 11d  are each independently selected from hydrogen, optionally substituted C 1-6  alkyl, and optionally substituted aryl which may be substituted by 0-5 moieties; 
         R 12a , R 12b , R 12c , and R 12d  are each independently selected from hydrogen, halogen, optionally substituted C 1-6  alkyl, optionally substituted branched C 1-6  alkyl, and optionally substituted C 1-6  alkoxy; 
         R 13  is independently selected at each occurrence from a group consisting of optionally substituted C 1-10  alkyl, optionally substituted branched C 1-10  alkyl, optionally substituted C3-8 cycloalkyl, and optionally substituted aryl which may be substituted by 0-5 moieties; 
         R 14  is selected from a group consisting of optionally substituted C 1-10  alkyl, optionally substituted branched C 1-10  alkyl, optionally substituted C 3-14  cycloalkyl, optionally substituted aryl which may be substituted by 0-5 moieties, optionally substituted benzyl which may be substituted by 0-5 moieties, —CH 2 OR 16 , CH(CH 3 )OR 16 , CH 2 SR 16 , CH 2 CH 2 SCH 3 , CH 2 CH 2 CH 2 CH 2 NR 17a R 17b , CH 2 COR 18 , CH 2 CH 2 COR 18 , 
       
       
         
           
           
               
               
           
         
         R 15  is selected from a group consisting of COR 6 , CO 2 R 7 , SO 2 R 8 , CONHR 9 , and P(O)(OR 10 ) 2 ; 
         R 16  is selected from the group consisting of hydrogen, optionally substituted C 1-10  alkyl, and optionally substituted branched C 1-10  alkyl; 
         R 17a  is selected from the group consisting of hydrogen, optionally substituted C 1-10  alkyl, and optionally substituted branched C 1-10  alkyl; 
         R 17b  is selected from the group consisting of hydrogen, optionally substituted C 1-10  alkyl, and optionally substituted branched C 1-10  alkyl; and 
         R 18  is selected from the group consisting of OH, NH 2 , and C 1-6  alkoxy; and 
         a hydrate, a solvate, a pharmaceutically acceptable salt, or a complex thereof. 
       
     
     
       2. The compound according to  claim 1 , wherein R 1  is COR 5 . 
     
     
       3. The compound according to  claim 1 , wherein R 2  is COR 5 . 
     
     
       4. The compound according to  claim 1 , wherein R 1  and R 2  are COR 5 . 
     
     
       5. The compound according to  claim 4 , wherein R 5  is OR 13 . 
     
     
       6. The compound according to  claim 5 , wherein R 3  is CONHR 9 . 
     
     
       7. The compound according to  claim 6 , wherein R 4  is optionally substituted C 3-6  cycloalkyl. 
     
     
       8. The compound according to  claim 7 , wherein R 9  is optionally substituted branched C 3-6  alkyl. 
     
     
       9. The compound according to  claim 1 , wherein R 5  is selected from: OR 13 ; 
       
         
           
           
               
               
           
         
       
     
     
       10. The compound according to  claim 9 , wherein R 13  is selected from: optionally substituted C 1-10  alkyl, optionally substituted branched C 1-10  alkyl, optionally substituted C 3-8  cycloalkyl, and optionally substituted aryl which may be substituted by 0-5 moieties. 
     
     
       11. The compound according to  claim 1 , wherein R 3  is selected from: optionally substituted C 1-6  alkyl, optionally substituted C 3-14  cycloalkyl, COR 6 , CO 2 R 7 , and CONHR 9 . 
     
     
       12. The compound according to  claim 1 , wherein R 3  is selected from: optionally substituted C 1-6  alkyl, optionally substituted C 3-8  cycloalkyl, and CONHR 9 . 
     
     
       13. The compound according to  claim 1 , wherein R 4  is selected from: optionally substituted C 1-6  alkyl, optionally substituted C 3-14  cycloalkyl, and optionally substituted aryl which may be substituted by 0-5 moieties. 
     
     
       14. The compound according to  claim 1 , wherein R 9  is selected from: hydrogen, optionally substituted C 1-10  alkyl, optionally substituted branched C 1-10  alkyl, and optionally substituted C3-14 cycloalkyl. 
     
     
       15. A compound according to  claim 1 , having the formula XXVIII(b): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
       16. A compound according to  claim 1 , having the formula XXX(a): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
       17. A composition comprising a compound according to  claim 1 , and a pharmaceutically acceptable carrier. 
     
     
       18. A method for treating a disease or condition associated with a virus selected from an arenavirus, a filovirus, a bunyavirus, and a flavivirus, wherein the disease or condition is selected from: Bovine viral diarrhea virus (BVDV); Dengue virus (DENV); Yellow fever virus (YFV); Ebola virus (EBoV); Marburg virus (MARV); Lassa fever virus (LFV); Tacaribe virus (TARV); and Rift Valley fever virus (RVFV), said method comprising administering to a subject in need thereof, an effective amount of a compound according to  claim 1 . 
     
     
       19. A compound of formula XXVII(a): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
       20. A compound of formula XXVIII(a): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof.